title: Persistence of minimal residual disease in bone marrow predicts outcome in follicular lymphomas treated with a rituximab-intensive program.
abstract: We assessed the prognostic value of minimal residual disease (MRD) within the ML17638 phase 3 trial from the Fondazione Italiana Linfomi, investigating the role of rituximab maintenance in elderly follicular lymphoma (FL) patients after a brief first-line chemoimmunotherapy. MRD for the bcl-2/IgH translocation was determined on bone marrow cells in a centralized laboratory belonging to the Euro-MRD consortium, using qualitative and quantitative polymerase chain reactions (PCRs). Of 234 enrolled patients, 227 (97%) were screened at diagnosis. A molecular marker (MM) was found in 51%. Patients with an MM were monitored at 8 subsequent times. Of the 675 expected follow-up samples, 83% were analyzed. Conversion to PCR negativity predicted better progression-free survival (PFS) at all post-treatment times (eg, end of therapy: 3-year PFS, 72% vs 39%; P < .007). MRD was predictive in both maintenance (83% vs 60%; P < .007) and observation (71% vs 50%; P < .001) groups. PCR positivity at the end of induction was an independent adverse predictor (hazard ratio, 3.1; 95% confidence interval, 1.36-7.07). MRD is a powerful independent outcome predictor in FL patients who receive rituximab-intensive programs, suggesting a need to investigate its value for decision-making. This trial was registered at www.clinicaltrial.gov as #NCT01144364.
authors.affiliation: Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin, Italy;
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.forename: Chiara
authors.initials: C
authors.lastname: Lobetti-Bodoni
authors.forename: Barbara
authors.initials: B
authors.lastname: Mantoan
authors.forename: Manuela
authors.initials: M
authors.lastname: Ceccarelli
authors.forename: Carola
authors.initials: C
authors.lastname: Boccomini
authors.forename: Elisa
authors.initials: E
authors.lastname: Genuardi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiappella
authors.forename: Luca
authors.initials: L
authors.lastname: Baldini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pulsoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Luigi
authors.initials: L
authors.lastname: Rigacci
authors.forename: Antonello
authors.initials: A
authors.lastname: Pinto
authors.forename: Sara
authors.initials: S
authors.lastname: Galimberti
authors.forename: Alessia
authors.initials: A
authors.lastname: Bari
authors.forename: Delia
authors.initials: D
authors.lastname: Rota-Scalabrini
authors.forename: Angela
authors.initials: A
authors.lastname: Ferrari
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaja
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallamini
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Francesca Gaia
authors.initials: FG
authors.lastname: Rossi
authors.forename: Enrica
authors.initials: E
authors.lastname: Gamba
authors.forename: Andrea
authors.initials: A
authors.lastname: Evangelista
authors.forename: Umberto
authors.initials: U
authors.lastname: Vitolo
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D060830:Consolidation Chemotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C582872:BCL2-IgH fusion protein, human; D015514:Oncogene Proteins, Fusion; D000069283:Rituximab